Compositions and methods for treatment of mammalian skin

ABSTRACT

Compositions useful for treatment of a wide range of skin disorders including: pre-cancerous lesions, keratotic lesions, superficial basal cell carcinomae; squamous cell carcinomae; malignant melanoma, and radiation-induced burns. In some embodiments the treatments comprise contacting human or other mammalian skin with a composition according to the disclosure. In other embodiments, administration of compositions provided is by injection. Some embodiments provide for preventive use of compositions provided towards preventing some forms of skin cancer and skin cancer-related disorders by repeated application to healthy-looking skin. Methods for providing the compositions are disclosed.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a Continuation of U.S. patent application Ser. No.12/661,567 filed Mar. 19, 2010, currently still pending, and claims thebenefit of U.S. Provisional Application No. 61/272,641 filed on Oct. 14,2009, the entire contents of each of which are hereby incorporatedherein by reference.

TECHNICAL FIELD

This invention relates generally to therapeutic, and other uses ofcompositions of matter, and to combinations including the compositions.In one narrower aspect, it relates to compositions useful for treatingor preventing certain pre-cancerous and cancerous conditions. In anothernarrower aspect it relates to topical treatments for variousskin-related ailments using compositions provided.

BACKGROUND OF THE INVENTION

Various compositions and materials have been proffered in the past asbeing beneficial in the treatment, alleviation, and prevention ofvarious skin-related and other bodily disorders. One broad class of suchmaterials are medicaments intended for topical use in the relief ofsymptoms of maladies such as basal cell carcinomae, actinic keratosis,and burns. Although there have been proposed many medicinal compositionsand materials for treating a wide range of symptoms and conditions, fewso far have proven efficacious and acceptable for alleviating thesymptoms of, or causing remissions in solar keratosis lesions present onmammalian skin and in particular in reference to human skin.

Acute radiation dermatitis is known to include skin burns which are anon-malignant side effect of external beam irradiation therapy.Radiation dermatitis is mitigated with a view towards preventing theonset of the condition in the first place, reducing the severity of theskin reaction, and the reduction of healing time for instances in whichit is manifest. There are few products or materials that successfullymitigate radiation dermatitis and other skin conditions arising fromexternal beam irradiation therapy are available in the marketplace.Physicians have typically had to resort to attempt to treating thecomplication of radiation dermatitis with symptomatic and homeopathicapplications that are limited in providing relief, resulting in arelatively low standard of care.

Cancer treatments using external beam irradiation are well known in theart to be the source of skin burns, particularly when anerythema-causing dose typically on the order of about 1.8 to 2.2 Gray(Gy) daily for multiple days of ionizing radiation is applied tomammalian skin, the erythemas presenting as red papules sometimesaccompanied by desquamation or blistering. Radiation employed inexternal beam irradiation is often derived from radioisotopes ofelements selected from the group consisting of: cobalt, cesium, iodine,platinum, and yttrium and is often a beta particle. Standardized dosesof particle emissions from decay of the selected radioisotope aresubsequently acted upon by a particle accelerator towards the target atthe time of therapy. Radiation employed in external beam irradiation isalso known to comprise irradiation of mammalian skin using photons,including infrared, visible, and ultraviolet light photons.

In general, when external beam irradiation is to be employed, dosagetreatment planning is done on an individual basis according toestablished patterns derived from clinical trials for specificconditions and diagnoses. In addition, calculated dosage variesdependently on the site of treatment. For example in some knowntreatment regimens for head and neck areas, the amount of radiationemployed is on the order of about 70 Gy. In some known treatmentregimens for breast areas the amount of radiation employed is on theorder of about 50-60 Gy. In some known treatment regimens forgastrointestinal tract areas the amount of radiation employed is on theorder of about 48 Gy. In some known treatment regimens employingexternal beam irradiation, standardized dosage patterns are from about1.8 to 2.2 Gy per day using fewer than 35 different treatment sessions,typically using dose fraction schedules with fractionation for known andacceptable doses being industry-standardized. In some known treatmentregimens employing external beam irradiation, a single frequency ofradiation is used, whereas in other regimens a plurality of frequenciesare simultaneously administered to the subject.

SUMMARY OF THE INVENTION

Methods are provided for alleviating symptoms induced by external beamirradiation on a mammalian subject. A method according to someembodiments comprises contacting a composition containing a hameliapatens extract to the skin of a mammalian subject in an effective amountand frequency for reducing symptoms from burns having resulted from aclinical exposure of external beam irradiation therapy.

Compositions used in some embodiments of alleviating symptoms induced byexternal beam irradiation comprise a pharmaceutically-acceptable carrierin combination with at least one material selected from the groupconsisting of: an alkaloid, pigenin-7-o-beta d-glucuronide; aricine;catequine; 24-methylenecycloartane-3β-ol; 24-methylcycloart-24-en-3β-ol;2 E-3,7,11,15,19-pentamethyl-2-eicosane-1-ol; ephedrine; flavonones;2′-5-5′-7-tetrahydroxy-7-o-rutinoside; isomaruquine; isopteropodine;maruquine; the methyl ester of maruquine; narirutin; narirutin (2r);narirutin (2s); oxindole alkaloids; oxindole aricine; palmirine;pteropodine; rumberine; rosmarinic acid; rotundic acid; rumberine;rutin; seneciophylline; β-sitosterol; speciophylline;stigmast-4-en-3-3-dione; stigmast-4-en-3-6-dione; stigmasterol; tannins;and ursolic acid, and including any mixtures thereof, present in aneffective amount for alleviating symptoms of said disorder.

DETAILED DESCRIPTION

This disclosure concerns the plant known as hamelia patens, its parts,their constituents, and extracts or concentrates prepared therefrom, aswell as certain particular therapeutic effects relating thereto. Hameliapatens is a perennial shrub or shrub-like plant that is sometimesreferred to as Scarlet Bush, Firebush, and Texas Firecracker, amongother common names. Hamelia patens grows in Florida, Texas, and othersouthern and southwestern states, and is also distributed throughoutcentral and south America. The plant has a woody stem and roots, broadleaves and at maturity produces bright red berries. An extract providedin accordance with this disclosure is produced using any combination ofparts of the hamelia patens plant, of any of its species, which partsare selected from the group consisting of: its roots, stems, leaves, andfruit.

A hamelia patens extract in some embodiments according to thisdisclosure is provided by first picking leaves from a species of theplant, the species in one non-limiting embodiment being hamelia patensjacq. In one embodiment about 509 grams of freshly-picked leaves ofHamelia Patens Jacq. were procured from hamelia patens jacq. grown inTexas. Stems were removed from the leaves and the leafy material was cuttransversely into strips. The cut leafy material was combined with about475 milliliters of CETAPHIL® gentle skin cleanser (GaldermaLaboratories) in a covered one-liter beaker and blended using a stirringrod until the leafy material was evenly distributed throughout the bulkof the composition. The contents of the beaker were heated to 65.5degrees centigrade for 30 minutes with frequent stirring. During thecourse of the heating the leaves turned to a dull green with a browncast. At the end of the 30 minutes the leafy material was compactedusing a potato masher, to squeeze more of the plant-borne matter fromthe leaves and into the bulk of the composition. Finally, the beaker'scontents were poured through a stainless steel screen, of sufficientmesh to separate the solid matter including leaves from the liquidportion, which liquid portion itself was subsequently strained throughcheesecloth, thus providing a liquid hamelia patens extract according toone embodiment of the disclosure.

In other embodiments of providing a hamelia patens extract, a proticsolvent such as water, or a lower alcohol, or a mixture comprising aplurality of lower alcohols, or blends comprising one or a plurality oflower alcohols and water, when miscible, in any relative proportions, isemployed as a liquid solvent into which the plants' constituents areextracted. In some embodiments the lower alcohol is any alcohol selectedfrom any C1-C4 alcohol, including any mixtures thereof, independentlypresent in any proportion. In some embodiments a water/alcohol mixturecontaining any amount in the range from about 5% to about 10% by volumeof the alcohol in water is used as a solvent. Various extractiontechniques known in the art may be employed, including percolation,soxhlet, and other extraction techniques, including those employingsupercritical carbon dioxide. In one embodiment about 500 grams ofground hamelia patens leaves are combined with about 500 ml of a mixturethat is 10% by volume of ethanol and 90% by volume of water, and heatedto about 65 degrees centigrade for 30 minutes. In alternate embodiments,the solvent is maintained at room temperature and the mixture of plantmatter and solvent is permitted to percolate for an extended time, of upto about 24 hours. In other embodiments, a longer extraction time in therange of between about 24 hours and about 72 hours is employed. Theresulting solution from such heating, percolation, or other extractiontechnique is centrifuged (optionally) and filtered to provide a liquidsolution hamelia patens extract. This solution extract is in oneembodiment applied as-is to mammalian skin. In alternate embodimentsvarious other materials may be combined with such solution extract toform skin creams, etc., as described below prior to its application tomammalian skin. In some embodiments, the solvent present in such aliquid solution extract is removed using techniques known to thoseskilled in the art (including reduced pressure distillation, flashevaporation, etc.) to yield a crystalline extract in the form of a drypowder. In some embodiments, the temperature of the liquid solventextract is not permitted to exceed about 50 degrees centigrade duringsolvent removal. In one embodiment when a solvent comprising 10% byvolume ethanol in 90% by volume water is employed at room temperature ina percolation lasting about 24 hours, the yield of dry crystallinehamelia patens extract provided following solvent removal amounts toabout 7% by weight based on the weight of the fresh-cut hamelia patensleaves employed. Typically by such processing the yield of crystallinehamelia patens extract ranges from between about 2% to about 8% byweight based on the weight of the plant matter used. While crystallineextracts are mentioned herein, it is understood by those skilled in theart that extracts obtained following solvent removal may not always becrystalline or powdered crystalline in nature owing to variation amongindividual plants' growing condition, time of harvest, and genetics,which can impact polymeric residues present. Thus in some embodiments anon-completely-crystalline residue may be obtained, such aspartially-gummy residues; however in general such non-completelycrystalline extracts obtained are substantially functionally-equivalentto a crystalline extract and are to be treated herein as beingsynonymous therewith for purposes of this specification and claimsappended hereto.

From dry powdered crystalline extract(s), compositions according to thedisclosure are prepared by mixing such extract(s) with various othermaterials, as desired. In some embodiments the crystalline hameliapatens extract is ground with a mortar or otherwise pulverized andcombined with or formulated into a skin crème or skin lotion at anydesired concentration, which concentration of crystalline hamelia patensextract is between about 0.05% by weight and about 85% by weight basedon the weight of the final composition, including all weight percentagesand ranges of weight percentages therebetween. In some embodiments thecrystalline hamelia patens extract is blended with at least one othermaterial that is a solid or liquid at room temperature, in any amount,in order to provide an extract concentrate. Such at least one othermaterial in some embodiments comprises a material selected from thegroup consisting of: silicates, aluminosilicates and silica present ineffective flow-enhancing amounts to enable the crystalline extract toflow freely when poured. In other embodiments, a crystalline hameliapatens extract according to the disclosure is combined with a solvent,to provide a solution that comprises an extract concentrate, in anyamount between about 1% by weight based on the total weight of theconcentrate, up to the saturation limit of the crystalline extract inthe solvent employed at ambient temperatures.

In some embodiments a crystalline hamelia patens extract so obtained iscombined with a glyceryl ester based oil that is plant-derived, and insome embodiments with a mixture of such glyceryl ester based oils.Suitable glyceryl ester based oils include without limitation oils suchas soybean oil, coconut oil, palm oil, corn oil, olive oil, sunfloweroil, safflower oil, cottonseed oil, rape oil, almond oil, sesame oil,peanut oil, and mixtures thereof in any proportion. A compositionaccording to some embodiments of this disclosure includes thecrystalline hamelia patens extract in combination with a plant-derivedoil (alternately mixtures including a plurality of such oils, eachpresent in any proportion), wherein the crystalline extract of hameliapatens is present in any amount between about 0.05% by weight to about85% by weight, based on the total weight of the composition, includingall percentages by weight and ranges of percentages by weighttherebetween. The presence of a fatty acid ester type oil as a vehiclein general is capable of facilitating transdermal passage of at leastone component material present in hamelia patens extract into andthrough mammalian skin. As used in this disclosure, mammalian skinincludes human skin, and mammalian subjects include human subjects.

In other embodiments, the crystalline hamelia patens extract is combinedwith water or a water/alcohol mixture as described above to providefurther compositions according to the disclosure. Compositions accordingto some embodiments of the disclosure include a crystalline hameliapatens extract in combination with water, and in alternate embodimentsin combination with water/alcohol mixtures, and in these aqueous andaqueous alcohol embodiments the crystalline hamelia patens extract ispresent in any amount between about 0.05% by weight and about 85% byweight, based on the total weight of the composition, including allpercentages by weight and ranges of percentages by weight therebetween.In different embodiments any C1 to C4 alcohol (including any mixturesthereof in any proportion) are used, either mixed with water in anychosen proportion, or substantially anhydrous.

In another embodiment, about a one-liter volume of cut hamelia patensleaves are compressed and combined with about 125 ml of petrolatum, themixture being heated to any temperature in the range of between aboutsixty (60) degrees centigrade and about eighty (80) degrees centigradefor about 10 minutes. This provides a hydrocarbon base containinghamelia patens extract that is in some embodiments able to be applieddirectly to mammalian skin, or alternately is useful in preparingcompositions according to other embodiments of this disclosure. In oneembodiment this petrolatum-borne extract is combined with effectiveamounts of one (and alternately any number more than one) of ananti-inflammatory, anti-oxidant, and/or anti-bacterial material toprovide an enhanced hamelia patens extract. Such a petrolatum-bornehamelia patens extract is easy to handle enabling quick and readyblending with other materials. In addition, petrolatum itself is notabsorbed by the skin. In other embodiments, the powdered crystallinehamelia patens extract referred to above is combined with petrolatum andheated with agitation to provide a composition according to thedisclosure wherein the crystalline extract of hamelia patens is presentin any amount between about 0.05% by weight to about 85% by weight,based on the total weight of the petrolatum-based composition, includingall percentages by weight and ranges of percentages by weighttherebetween.

In another embodiment, a liquid solution hamelia patens extract, (forexample prepared by combining hamelia patens plant parts with a solventand percolating at about 60 degrees centigrade) wherein the solvent is a90% water/10% ethanol (by volume) mixture is combined with any vegetableoil to provide a mixture that is heated with stirring sufficiently tosimmer off the water and alcohol present, causing the hamelia patensextract to be taken up into the oil. For such embodiments, the quantityof water/ethanol extract and oil used are selected to provide an amountof crystalline hamelia patens extract present in the final compositionin any amount between about 0.05% by weight and about 85% by weight,based on the total weight of the composition, including all percentagesby weight and ranges of percentages by weight therebetween. In alternateembodiments, one begins with the crystalline hamelia patens extract anddissolves it in water/ethanol mixture comprising about 10% ethanol byvolume and once dissolved, this mixture is combined with any desiredamount of oil, the water/ethanol present is subsequently simmered off byheating to afford an oil-borne hamelia patens extract.

Thus, the present disclosure in some embodiments provides compositionscomprising a crystalline hamelia patens extract in combination with atleast one material selected from the group consisting of: water,water/alcohol mixtures, hydrocarbons (petrolatum) and ester-type fats oroils, wherein the hamelia patens extract is present in any amountbetween about 0.05% by weight to about 85% by weight, based on the totalweight of the composition, including all percentages by weight andranges of percentages by weight therebetween.

Crystalline or liquid (including aqueous, non-aqueous, alcoholic,hydrocarbon-based, and oil-borne) hamelia patens extracts as providedherein may be further refined to isolate or concentrate any one, or morethan one, of the compounds present in hamelia patens using methods ortechniques generally known to those skilled in the art.

A hamelia patens extract provided according to some embodiments of thedisclosure contains at least any one compound, and in other embodimentscontains any mixture comprising a plurality including any two or morethan two compounds present in the listing now set forth, the compoundsin such listing comprising: alkaloids, 2-alpha-hydroxyursolic acid,apigenin-7-o-beta d-glucuronide, aricine, catequine, 19-alphahydroxyAsiatic acid, 24-methylenecycloartane-3β-ol,24-methylcycloart-24-en-3β-ol, 2E-3,7,11,15,19-pentamethyl-2-eicosane-1-ol, ephedrine, flavonones,2′-5-5′-7-tetrahydroxy-7-o-rutinoside, isomaruquine, isopteropodine,maruquine, the methyl ester of maruquine, mitraphylline, narirutin,narirutin (2r), narirutin (2s), oxindole alkaloids, oxindole aricine,palmirine, pigenin-7-o-beta D-glucuronide, pomolic acid, pteropodine,rumberine, rosmarinic acid, rotundic acid, rumberine, rutin,seneciophylline, β-sitosterol, speciophylline, stigmast-4-en-3-3-dione,stigmast-4-en-3-6-dione, stigmasterol, tannins, tormentic acid, uncarineF, and ursolic acid. In some embodiments, all of these compounds arepresent in a hamelia patens extract useful for providing a compositionaccording to this disclosure.

Accordingly, a hamelia patens extract as provided in some embodimentscontains alkaloids. In some embodiments alkaloids are present in acomposition according to the disclosure in any amount between about0.05% and about 30% by weight based on the total weight of thecomposition, including all weight percents and ranges of weight percentstherebetween. A hamelia patens extract as provided in some embodimentscontains apigenin-7-o-beta d-glucuronide. In some embodimentsapigenin-7-o-beta d-glucuronide is present in a composition according tothe disclosure in any amount between about 0.05% and about 30% by weightbased on the total weight of the composition, including all weightpercents and ranges of weight percents therebetween. A hamelia patensextract as provided in some embodiments contains aricine. In someembodiments aricene is present in a composition according to thedisclosure in any amount between about 0.05% and about 30% by weightbased on the total weight of the composition, including all weightpercents and ranges of weight percents therebetween. A hamelia patensextract as provided in some embodiments contains catequine. In someembodiments catequine is present in a composition according to thedisclosure in any amount between about 0.05% and about 30% by weightbased on the total weight of the composition, including all weightpercents and ranges of weight percents therebetween. A hamelia patensextract as provided in some embodiments contains24-methylenecycloartane-3β-ol. In some embodiments24-methylenecycloartane-3β-ol is present in a composition according tothe disclosure in any amount between about 0.05% and about 30% by weightbased on the total weight of the composition, including all weightpercents and ranges of weight percents therebetween. A hamelia patensextract as provided in some embodiments contains24-methylcycloart-24-en-3β-ol. In some embodiments24-methylcycloart-24-en-3β-ol is present in a composition according tothe disclosure in any amount between about 0.05% and about 30% by weightbased on the total weight of the composition, including all weightpercents and ranges of weight percents therebetween. A hamelia patensextract as provided in some embodiments contains 2E-3,7,11,15,19-pentamethyl-2-eicosane-1-ol. In some embodiments 2E-3,7,11,15,19-pentamethyl-2-eicosane-1-ol is present in a compositionaccording to the disclosure in any amount between about 0.05% and about30% by weight based on the total weight of the composition, includingall weight percents and ranges of weight percents therebetween. Ahamelia patens extract as provided in some embodiments containsephedrine. In some embodiments ephedrine is present in a compositionaccording to the disclosure in any amount between about 0.05% and about30% by weight based on the total weight of the composition, includingall weight percents and ranges of weight percents therebetween. Ahamelia patens extract as provided in some embodiments containsflavonones. In some embodiments flavonones are present in a compositionaccording to the disclosure in any amount between about 0.05% and about30% by weight based on the total weight of the composition, includingall weight percents and ranges of weight percents therebetween. Ahamelia patens extract as provided in some embodiments contains2′-5-5′-7-tetrahydroxy-7-o-rutinoside. In some embodiments2′-5-5′-7-tetrahydroxy-7-o-rutinoside is present in a compositionaccording to the disclosure in any amount between about 0.05% and about30% by weight based on the total weight of the composition, includingall weight percents and ranges of weight percents therebetween. Ahamelia patens extract as provided in some embodiments contains19-alpha-hydroxy asiatic acid. In some embodiments 19-alpha-hydroxyasiatic acid is present in a composition according to the disclosure inany amount between about 0.05% and about 30% by weight based on thetotal weight of the composition, including all weight percents andranges of weight percents therebetween. A hamelia patens extract asprovided in some embodiments contains isomaruquine. In some embodimentsisomaruquine is present in a composition according to the disclosure inany amount between about 0.05% and about 30% by weight based on thetotal weight of the composition, including all weight percents andranges of weight percents therebetween. A hamelia patens extract asprovided in some embodiments contains isopteropodine. In someembodiments isopteropodine is present in a composition according to thedisclosure in any amount between about 0.05% and about 30% by weightbased on the total weight of the composition, including all weightpercents and ranges of weight percents therebetween. A hamelia patensextract as provided in some embodiments contains maruquine. In someembodiments maruquine is present in a composition according to thedisclosure in any amount between about 0.05% and about 30% by weightbased on the total weight of the composition, including all weightpercents and ranges of weight percents therebetween. A hamelia patensextract as provided in some embodiments contains the methyl ester ofmaruquine. In some embodiments the methyl ester of maruquine is presentin a composition according to the disclosure in any amount between about0.05% and about 30% by weight based on the total weight of thecomposition, including all weight percents and ranges of weight percentstherebetween. A hamelia patens extract as provided in some embodimentscontains mitraphylline. In some embodiments mitraphylline is present ina composition according to the disclosure in any amount between about0.05% and about 30% by weight based on the total weight of thecomposition, including all weight percents and ranges of weight percentstherebetween. A hamelia patens extract as provided in some embodimentscontains narirutin. In some embodiments narirutin is present in acomposition according to the disclosure in any amount between about0.05% and about 30% by weight based on the total weight of thecomposition, including all weight percents and ranges of weight percentstherebetween. A hamelia patens extract as provided in some embodimentscontains narirutin (2r). In some embodiments narirutin (2r) is presentin a composition according to the disclosure in any amount between about0.05% and about 30% by weight based on the total weight of thecomposition, including all weight percents and ranges of weight percentstherebetween. A hamelia patens extract as provided in some embodimentscontains narirutin (2s). In some embodiments narirutin (2s) is presentin a composition according to the disclosure in any amount between about0.05% and about 30% by weight based on the total weight of thecomposition, including all weight percents and ranges of weight percentstherebetween. A hamelia patens extract as provided in some embodimentscontains oxindole alkaloids. In some embodiments oxindole alkaloids arepresent in a composition according to the disclosure in any amountbetween about 0.05% and about 30% by weight based on the total weight ofthe composition, including all weight percents and ranges of weightpercents therebetween. A hamelia patens extract as provided in someembodiments contains oxindole In some embodiments oxindole aricine ispresent in a composition according to the disclosure in any amountbetween about 0.05% and about 30% by weight based on the total weight ofthe composition, including all weight percents and ranges of weightpercents therebetween. A hamelia patens extract as provided in someembodiments contains palmirine. In some embodiments palmirine is presentin a composition according to the disclosure in any amount between about0.05% and about 30% by weight based on the total weight of thecomposition, including all weight percents and ranges of weight percentstherebetween. A hamelia patens extract as provided in some embodimentscontains pigenin-7-o-beta D-glucuronide. In some embodimentspigenin-7-o-beta D-glucuronide is present in a composition according tothe disclosure in any amount between about 0.05% and about 30% by weightbased on the total weight of the composition, including all weightpercents and ranges of weight percents therebetween. A hamelia patensextract as provided in some embodiments contains pomolic acid. In someembodiments pomolic acid is present in a composition according to thedisclosure in any amount between about 0.05% and about 30% by weightbased on the total weight of the composition, including all weightpercents and ranges of weight percents therebetween. A hamelia patensextract as provided in some embodiments contains pteropodine. In someembodiments pteropodine is present in a composition according to thedisclosure in any amount between about 0.05% and about 30% by weightbased on the total weight of the composition, including all weightpercents and ranges of weight percents therebetween. A hamelia patensextract as provided in some embodiments contains rumberine. In someembodiments rumberine is present in a composition according to thedisclosure in any amount between about 0.05% and about 30% by weightbased on the total weight of the composition, including all weightpercents and ranges of weight percents therebetween. A hamelia patensextract as provided in some embodiments contains rosmarinic acid. Insome embodiments rosmarinic acid is present in a composition accordingto the disclosure in any amount between about 0.05% and about 30% byweight based on the total weight of the composition, including allweight percents and ranges of weight percents therebetween. A hameliapatens extract as provided in some embodiments contains rotundic acid.In some embodiments rotundic acid is present in a composition accordingto the disclosure in any amount between about 0.05% and about 30% byweight based on the total weight of the composition, including allweight percents and ranges of weight percents therebetween. A hameliapatens extract as provided in some embodiments contains rumberine. Insome embodiments rumberine is present in a composition according to thedisclosure in any amount between about 0.05% and about 30% by weightbased on the total weight of the composition, including all weightpercents and ranges of weight percents therebetween. A hamelia patensextract as provided in some embodiments contains rutin. In someembodiments rutin is present in a composition according to thedisclosure in any amount between about 0.05% and about 30% by weightbased on the total weight of the composition, including all weightpercents and ranges of weight percents therebetween. A hamelia patensextract as provided in some embodiments contains seneciophylline. Insome embodiments seneciophylline is present in a composition accordingto the disclosure in any amount between about 0.05% and about 30% byweight based on the total weight of the composition, including allweight percents and ranges of weight percents therebetween. A hameliapatens extract as provided in some embodiments contains β-sitosterol. Insome embodiments β-sitosterol is present in a composition according tothe disclosure in any amount between about 0.05% and about 30% by weightbased on the total weight of the composition, including all weightpercents and ranges of weight percents therebetween. A hamelia patensextract as provided in some embodiments contains speciophylline. In someembodiments speciophylline is present in a composition according to thedisclosure in any amount between about 0.05% and about 30% by weightbased on the total weight of the composition, including all weightpercents and ranges of weight percents therebetween. A hamelia patensextract as provided in some embodiments containsstigmast-4-en-3-3-dione. In some embodiments stigmast-4-en-3-3-dione ispresent in a composition according to the disclosure in any amountbetween about 0.05% and about 30% by weight based on the total weight ofthe composition, including all weight percents and ranges of weightpercents therebetween. A hamelia patens extract as provided in someembodiments contains stigmast-4-en-3-6-dione. In some embodimentsstigmast-4-en-3-6-dione is present in a composition according to thedisclosure in any amount between about 0.05% and about 30% by weightbased on the total weight of the composition, including all weightpercents and ranges of weight percents therebetween. A hamelia patensextract as provided in some embodiments contains stigmasterol. In someembodiments stigmasterol is present in a composition according to thedisclosure in any amount between about 0.05% and about 30% by weightbased on the total weight of the composition, including all weightpercents and ranges of weight percents therebetween. A hamelia patensextract as provided in some embodiments contains tannins. In someembodiments tannins are present in a composition according to thedisclosure in any amount between about 0.05% and about 30% by weightbased on the total weight of the composition, including all weightpercents and ranges of weight percents therebetween. A hamelia patensextract as provided in some embodiments contains tormentic acid. In someembodiments tormentic acid is present in a composition according to thedisclosure in any amount between about 0.05% and about 30% by weightbased on the total weight of the composition, including all weightpercents and ranges of weight percents therebetween. A hamelia patensextract as provided in some embodiments contains uncarine F. In someembodiments uncarine F is present in a composition according to thedisclosure in any amount between about 0.05% and about 30% by weightbased on the total weight of the composition, including all weightpercents and ranges of weight percents therebetween. A hamelia patensextract as provided in some embodiments contains ursolic acid. In someembodiments ursolic acid is present in a composition according to thedisclosure in any amount between about 0.05% and about 30% by weightbased on the total weight of the composition, including all weightpercents and ranges of weight percents therebetween. A hamelia patensextract as provided in some embodiments contains 2-alpha-hydroxy ursolicacid. In some embodiments 2-alpha-hydroxy ursolic acid is present in acomposition according to the disclosure in any amount between about0.05% and about 30% by weight based on the total weight of thecomposition, including all weight percents and ranges of weight percentstherebetween. Terms including “about” when used herein, such as “about30%”, are understood as also including the exact numerical valueoccurring immediately subsequent to “about”, in the same context, i.e.,such a recitation as “about 30%” includes the exact value specified, inthis instance exactly 30%. In some embodiments, each of the componentmaterials in the listing above, when present in a hamelia patensextract, are present in amounts within their specified rangesindependently with respect to the amounts of the other componentspresent.

As concerns any one or more than one of the foregoing materials in saidlisting which are described as being acids, the present disclosureincludes the presence of such materials in their neutralized forms, andin alternate embodiments their esterified forms condensed with anyalcohol or polyol. For those component compounds in the listing having acarboxylic acids function, the present disclosure includes the presenceof such materials in their anionic forms, including without limitationtheir alkali metal salts, alkaline earth salts, ammonium salts andsubstituted ammonium salts, the concentration of the anionic forms ofsuch material(s) being present in a composition according to thedisclosure in the amounts specified for the acid form of thematerial(s). In some embodiments the concentration ranges for componentspresent in a composition according to the disclosure are applied basedon the weight percent of the anionic form of the material. In someembodiments, the concentration ranges in a composition according to thedisclosure are determined based on the weight percent of the salt,including the cation present. Likewise when basic substances arerecited, the present disclosure includes the presence of such materialsin their protonated forms, the concentration ranges of such materialsbeing present in a composition according to the disclosure in theamounts specified above for the basic form. In some embodiments theconcentration ranges for a composition according to the disclosure isdetermined based on the weight percent of the protonated form of thematerial present. In some embodiments, the concentration ranges for acomposition according to the disclosure is determined based on theweight percent of the protonated form of the material and including itsanion present for charge neutrality present.

In some embodiments, all of the materials in the above listing arepresent in a composition according to the disclosure. In otherembodiments any one or more than one of the materials in the abovelisting are independently be omitted from the contents of a compositionaccording to the disclosure, such as by refining a hamelia patensextract (including a crystalline hamelia patens extract) for the purposeof removal of one, or any number greater than one, of materials in theabove listing present in the extract using techniques known to thoseskilled in the art. In other embodiments any one or any number greaterthan one of such components present in the listing may be purified usingtechniques known to those of ordinary skill in the art. For example, toremove nitrogenous bases the extract material is put up into aqueoussolution and made alkaline, and extraction done using CHCl3 to removeamino compounds, the aqueous layer being subsequently re-acidified orneutralized. In one embodiment, ammonia is used to make the materialalkaline for purposes of such extraction, which ammonia is subsequentlyremoved after the extraction having been completed by blowing withnitrogen or treatment to reduced pressure. In another embodiment anaqueous extract of hamelia patens is made slightly acidic by addition ofHCl, and extractions are done using ethyl acetate, ether, chloroform,and/or hexanes. Following extraction, the aqueous layer is subjected toreduced pressure and slight heating or a sweep of nitrogen or otherinert gas to facilitate removal of the HCl. In such embodiments,fractions obtained may be further treated to selectively separate orremove component materials present, using techniques known in the artincluding without limitation such techniques as preparatorychromatography columns, fractional distillation under vacuo, moleculardistillation, precipitation and filtration, etc. In further embodiments,one or more than one of any of the above-named components in the listingare produced synthetically or are otherwise acquired or produced, andare subsequently blended with one another to provide a blend thatcomprises a synthetic hamelia patens extract that is useful in providinga composition according to the disclosure, such components that areselected to be present each being individually present at levels withinthe ranges specified herein.

An extract of the plant hamelia patens according to some embodiments ofthe disclosure may thus comprise a crude (water-based, H2O/alcoholbased, oil-based, or petrolatum based) hamelia patens extract from whichany one, or any combination including any number more than one of, thecomponent materials set forth in the listing above are omitted orremoved from said extract, the resulting extract being useful forproviding a composition according to this disclosure. In someembodiments at least any chosen two of the component materials selectedfrom the group consisting of the materials recited in the listing aboveremain or are present in a hamelia patens extract useful for providing acomposition according to this disclosure, the component materials beingindependently present at concentrations within any of the rangesspecified above in such compositions or extracts. In some embodiments atleast any chosen three of the component materials selected from thegroup consisting of the materials recited in the listing above remain orare present in a hamelia patens extract useful for providing acomposition according to this disclosure, the component materials beingindependently present at concentrations within the ranges specifiedabove in such compositions or extracts. In some embodiments at least anychosen four of the component materials selected from the groupconsisting of the materials recited in the listing above remain or arepresent in a hamelia patens extract useful for providing a compositionaccording to this disclosure, the component materials beingindependently present at concentrations within the ranges specifiedabove in such composition or extracts. In some embodiments at least anychosen five of the component materials selected from the groupconsisting of the materials recited in the listing above remain or arepresent in a hamelia patens extract useful for providing a compositionaccording to this disclosure, the component materials beingindependently present at concentrations within the ranges specifiedabove in such compositions or extracts.

This disclosure includes hamelia patens extracts from which some of thecomponents in the listing above have been removed, and also hameliapatens extracts comprising a plurality of the materials in the listingabove which are produced by combining previously-isolated purifiedcomponent materials from such listing. In some embodiments, allalkaloids are omitted or removed when providing a hamelia patens extractaccording to the disclosure, the remaining components of the listingremaining present. In some embodiments, all 2-alpha-hydroxyursolic acidis omitted or removed when providing a hamelia patens extract accordingto the disclosure, the remaining components of the listing remainingpresent. In some embodiments, all flavonones are omitted or removed whenproviding a hamelia patens extract according to the disclosure, theremaining components of the listing remaining present. In someembodiments, all apigenin-7-o-beta d-glucuronide is omitted or removedwhen providing a hamelia patens extract according to the disclosure, theremaining components of the listing remaining present. In someembodiments, all aricine is omitted or removed when providing a hameliapatens extract according to the disclosure, the remaining components ofthe listing remaining present. In some embodiments, all catequine isomitted or removed when providing a hamelia patens extract according tothe disclosure, the remaining components of the listing remainingpresent. In some embodiments, all flavonones is omitted or removed whenproviding a hamelia patens extract according to the disclosure, theremaining components of the listing remaining present. In someembodiments, all 19-alphahydroxy Asiatic acid is omitted or removed whenproviding a hamelia patens extract according to the disclosure, theremaining components of the listing remaining present. In someembodiments, all 24-methylenecycloartane-3β-ol is omitted or removedwhen providing a hamelia patens extract according to the disclosure, theremaining components of the listing remaining present. In someembodiments, all 24-methylcycloart-24-en-3β-ol is omitted or removedwhen providing a hamelia patens extract according to the disclosure, theremaining components of the listing remaining present. In someembodiments, all 2 E-3,7,11,15,19-pentamethyl-2-eicosane-1-ol is omittedor removed when providing a hamelia patens extract according to thedisclosure, the remaining components of the listing remaining present.In some embodiments, all ephedrine is omitted or removed when providinga hamelia patens extract according to the disclosure, the remainingcomponents of the listing remaining present. In some embodiments, all2′-5-5′-7-tetrahydroxy-7-o-rutinoside is omitted or removed whenproviding a hamelia patens extract according to the disclosure, theremaining components of the listing remaining present. In someembodiments, all flavonones are omitted or removed when providing ahamelia patens extract according to the disclosure, the remainingcomponents of the listing remaining present. In some embodiments, allisomaruquine is omitted or removed when providing a hamelia patensextract according to the disclosure, the remaining components of thelisting remaining present. In some embodiments, all isopteropodine isomitted or removed when providing a hamelia patens extract according tothe disclosure, the remaining components of the listing remainingpresent. In some embodiments, all maruquine is omitted or removed whenproviding a hamelia patens extract according to the disclosure, theremaining components of the listing remaining present. In someembodiments, all the methyl ester of maruquine is omitted or removedwhen providing a hamelia patens extract according to the disclosure, theremaining components of the listing remaining present. In someembodiments, all mitraphylline is omitted or removed when providing ahamelia patens extract according to the disclosure, the remainingcomponents of the listing remaining present. In some embodiments, allnarirutin is omitted or removed when providing a hamelia patens extractaccording to the disclosure, the remaining components of the listingremaining present. In some embodiments, all narirutin (2r) is omitted orremoved when providing a hamelia patens extract according to thedisclosure, the remaining components of the listing remaining present.In some embodiments, all narirutin (2s) is omitted or removed whenproviding a hamelia patens extract according to the disclosure, theremaining components of the listing remaining present. In someembodiments, all oxindole alkaloids are omitted or removed whenproviding a hamelia patens extract according to the disclosure, theremaining components of the listing remaining present. In someembodiments, all oxindole aricine is omitted or removed when providing ahamelia patens extract according to the disclosure, the remainingcomponents of the listing remaining present. In some embodiments, allpalmirine is omitted or removed when providing a hamelia patens extractaccording to the disclosure, the remaining components of the listingremaining present. In some embodiments, all pigenin-7-o-betaD-glucuronide is omitted or removed when providing a hamelia patensextract according to the disclosure, the remaining components of thelisting remaining present. In some embodiments, all pomolic acid isomitted or removed when providing a hamelia patens extract according tothe disclosure, the remaining components of the listing remainingpresent. In some embodiments, all pteropodine is omitted or removed whenproviding a hamelia patens extract according to the disclosure, theremaining components of the listing remaining present. In someembodiments, all rumberine is omitted or removed when providing ahamelia patens extract according to the disclosure, the remainingcomponents of the listing remaining present. In some embodiments, allrosmarinic acid is omitted or removed when providing a hamelia patensextract according to the disclosure, the remaining components of thelisting remaining present. In some embodiments, all rotundic acid isomitted or removed when providing a hamelia patens extract according tothe disclosure, the remaining components of the listing remainingpresent. In some embodiments, all rutin is omitted or removed whenproviding a hamelia patens extract according to the disclosure, theremaining components of the listing remaining present. In someembodiments, all seneciophylline is omitted or removed when providing ahamelia patens extract according to the disclosure, the remainingcomponents of the listing remaining present. In some embodiments, allβ-sitosterol is omitted or removed when providing a hamelia patensextract according to the disclosure, the remaining components of thelisting remaining present. In some embodiments, all speciophylline isomitted or removed when providing a hamelia patens extract according tothe disclosure, the remaining components of the listing remainingpresent. In some embodiments, all stigmast-4-en-3-3-dione is omitted orremoved when providing a hamelia patens extract according to thedisclosure, the remaining components of the listing remaining present.In some embodiments, all stigmast-4-en-3-6-dione is omitted or removedwhen providing a hamelia patens extract according to the disclosure, theremaining components of the listing remaining present. In someembodiments, all stigmasterol is omitted or removed when providing ahamelia patens extract according to the disclosure, the remainingcomponents of the listing remaining present. In some embodiments, alltannins are omitted or removed when providing a hamelia patens extractaccording to the disclosure, the remaining components of the listingremaining present. In some embodiments, all tormentic acid is omitted orremoved when providing a hamelia patens extract according to thedisclosure, the remaining components of the listing remaining present.In some embodiments, all uncarine F is omitted or removed when providinga hamelia patens extract according to the disclosure, the remainingcomponents of the listing remaining present. In some embodiments, allursolic acid is omitted or removed when providing a hamelia patensextract according to the disclosure, the remaining components of thelisting remaining present. As a non-limiting example, in someembodiments, all flavones, all rutin, and ephedrine are removed oromitted, the remaining components of the listing remaining present in ahamelia patens extract according to this disclosure; however, any one orcombination including more than one material in the listing may beremoved or omitted. A combination, including a hamelia patens extract,according to the disclosure and useful in accordance with providingcompositions according to some embodiments of this disclosure may thuscontain any number between about one and about all of the foregoingmaterials in the listing, in any combination, each, when present, beingindependently present in any amount within the ranges specified above.

For some embodiments of the disclosure in which it is intended that ahamelia patens extract be contacted with mammalian skin, the extract ispresent in combination with other materials, of which petrolatum is onenon-limiting example. In some embodiments a hamelia patens extract(including those described above which omit one or more than onematerials from said listing) is present as a component of a mixturecomprising an effective amount of an pharmaceutically acceptablecarrier, which in some embodiments comprises a lotion, skin crème, orsalve. For these embodiments, “pharmaceutically-acceptable carrier” isused in its ordinary sense relative to the different embodiments herein,generally including pharmaceutically-acceptable, non-toxic diluents orvehicles useful in formulation of pharmaceutical compositions fortopical, oral, or basal layer injection to human or animal subjects.Pharmaceutically-acceptable carriers can include, without limitation,one or more than one materials selected from the group consisting ofbuffering agents, solubilizing agents, stabilizing agents, liquids suchas water, saline solution, glycerol and ethanol. Such carriers enable apharmaceutical composition to be formulated as tablets, pills, dragees,capsules, liquids, gels, syrups, slurries, suspensions, emulsions, andthe like for ingestion, injection, or topical application to mammalianskin. A discussion of pharmaceutically-acceptable carriers is availablein Remington's Pharmaceutical Sciences (Mack Pub. Co., N.J. 1991).

Only effective amounts of hamelia patens extracts are needed to preventor treat skin conditions such as pre-cancerous lesions, keratoticlesions, radiation-induced burns and other indications recited herein.Topical application to affected skin sites is accomplished in someembodiments by combination of the hamelia patens extract with a carrier,and particularly a carrier in which compounds present in the hameliapatens extract are soluble per se or are effectively solubilized (e.g.,as a solution, suspension, emulsion, or microemulsion), and contactingsuch combinations to mammalian skin. It is desirable that the carrier beinert in the sense of not bringing about a deactivation, reaction ordetrimental chemical change of any components present in a hameliapatens extract chosen to be present in the formulation, and in the senseof the carrier not bringing about any adverse effect on skin to which itis applied.

Thus, in some embodiments, suitable carriers of or for a hamelia patensextract are those which are pharmaceutically acceptable. Within thisclass are included water, water-based carriers, alcohols, alcohol-basedcarriers, oils, and oil-based carriers, mineral oil and petrolatum-basedcarriers chosen for their ability to dissolve or disperse componentspresent in the hamelia patens extract at concentrations suitable for usein therapeutic treatment of mammalian skin. In some embodiments,relatively low concentrations of hamelia patens extract or any of itsselected components in a combination according to the disclosure may beemployed for instances in which more frequent topical application isundertaken, versus the frequency of application of a compositionaccording to the disclosure in which the hamelia patens extract or anyof its selected components are present in relatively higher amounts. Insome embodiments a composition that is intended to be topically appliedis formulated to contain at least about 0.25% and up to about 25% byweight based on the total weight of the composition of crystallinehamelia patens extract, and accordingly carriers can be chosen which cansolubilize or disperse the components of the crystalline extract at suchconcentrations. In some embodiments, crystalline hamelia patens extractis present in a composition according to the disclosure in any amountbetween about 0.01% to about 30% by weight based on the total weight ofthe composition, including all percentages and ranges of percentagestherebetween. In some embodiments a composition according to thedisclosure contains about 10% by weight total crystalline hamelia patensextract.

While the carrier for extract of hamelia patens can consist of orcomprise a relatively simple solvent or dispersant such as oils, thecarrier may comprise materials that make a composition according to thisdisclosure more conducive to topical application, and particularlycarriers which aid in percutaneous delivery and penetration of at leastone in some embodiments, and in other embodiments a plurality ofcomponents of hamelia patens extract into dermal lipid layers. Many suchcompositions are known in the art, and can take the form of lotions,creams, gels or even solid compositions (e.g., stick-form preparations).Typical compositions include lotions containing water and/or alcoholsand emollients such as hydrocarbon oils and waxes, silicone oils,hyaluronic acid, vegetable, animal or marine fats or oils, glyceridederivatives, fatty acids or fatty acid esters or alcohols or alcoholethers, lanolin and derivatives, polyhydric alcohols or esters, waxesters, sterols, phospholipids and the like, and generally alsoemulsifiers (nonionic, cationic or anionic), although some of theemollients inherently possess emulsifying properties. These same generalingredients can be formulated into a crème rather than a lotion, or intogels, or into solid sticks by utilization of different proportions ofthe ingredients and/or by inclusion of thickening agents such as gums orother forms of hydrophilic colloids. Such compositions are within theclass of those comprising pharmaceutically-acceptable carriers. In someembodiments those most preferred for skin are those carriers which arefat-soluble, i.e., those which can effectively penetrate skin layers anddeliver the active hamelia patens extract or one or a plurality of itscomponents to the lipid-rich layers of the skin. In addition, a hameliapatens extract according to the disclosure may be applied using atime-release patch, as are used in hormone delivery, nicotine patches,anti-acne patches, and the like. Crèmes, aqueous solutions, pastes,powders, etc. are all suitable delivery vehicles for an extract ofhamelia patens or one or more of its components to mammalian skin, whichincludes human skin.

Thus, a hamelia patens extract of the present disclosure (which termincludes crystalline and other extracts, synthetically-assembled orotherwise provided), and alternately any of its components in anynumber, combination, and quantity as earlier set forth may be present ina wide range of compositions suitable to be applied to skin. Inaddition, a hamelia patens extract according to the present disclosuremay be present in combination with surfactants and materials which areused in personal care products, in which the level of hamelia patensextract ranges from about 1% to up to about 60% by weight based on thetotal weight of the composition, including all percentages and ranges ofpercentages therebetween.

To the extent that other materials present in a composition of thedisclosure with the hamelia patens extract may form binary activesystems, ternary active systems etc., in some embodiments the hameliapatens extract or component(s) thereof independently present in anyamount may comprise the majority of an anti-keratotic system or it maycomprise less than the majority of the anti-keratotic system.Surfactants and other materials which can be used in combination with ahamelia patens extract in forming personal care compositions accordingto this disclosure include without limitation: amphoteric/zwitterionicsurfactants; anionic surfactants; nonionic surfactants; cationicsurfactants; and optional ingredients, including without limitationthose described below.

Amphoteric surfactants suitable for inclusion in a composition accordingto this disclosure in combination with a hamelia patens extract or anyone or more than one of its components independently present in anyamount within the ranges specified above can broadly be described assurface active agents containing at least one anionic and one cationicgroup and can act as either acids or bases depending on pH. Some ofthese compounds are aliphatic derivatives of heterocyclic secondary andtertiary amines in which the aliphatic radical may be straight orbranched and wherein one of the aliphatic substituents contains fromabout 6 to about 20, preferably 8 to 18, carbon atoms and at least onecontains an anionic water-solubilizing group, e.g., carboxy,phosphonate, phosphate, sulfonate, sulfate.

Zwitterionic surfactants suitable for inclusion in a compositionaccording to this disclosure in combination with a hamelia patensextract or any of its components independently present in any amountspecified in the ranges above can be described as surface active agentshaving a positive and negative charge in the same molecule whichmolecule is zwitterionic at all pH's. Zwitterionic surfactants areexemplified by the betaines and the sultaines. The zwitterioniccompounds generally contain a quaternary ammonium, quaternaryphosphonium or a tertiary sulfonium moiety. The cationic atom in thequaternary compound can be part of a heterocyclic ring. In all of thesecompounds there is at least one aliphatic group, straight chain orbranched, containing from about 6 to 20, preferably 8 to 18, carbonatoms and at least one aliphatic substituent containing an anionicwater-solubilizing group, e.g., carboxy, sulfonate, sulfate, phosphateor phosphonate.

Examples of amphoteric and zwitterionic surfactants suitable forinclusion in a composition in combination with a hamelia patens extractor any of its components independently in any amount specified withinthe ranges above according to the present disclosure include the alkalimetal, alkaline earth metal, ammonium or substituted ammonium salts ofalkyl amphocarboxyglycinates and alkylamphocarboxypropionates, alkylamphodipropionates, alkyl monoacetate, alkyl diacetates,alkylamphoglycinates, and alkyl amphopropionates wherein alkylrepresents an alkyl group having from 6 to about 20 carbon atoms. Othersuitable surfactants include alkyliminomonoacetates,alkyliminidiacetates, alkyliminopropionates, alkyliminidipropionates,and alkylamphopropylsulfonates having between 12 and 18 carbon atoms,alkyl betaines and alkylamidoalkylene betaines and alkyl sultaines andalkylamidoalkylenehydroxy sulfonates.

Anionic surfactants suitable for inclusion in a composition incombination with a hamelia patens extract or any of its componentsindependently present in any amount specified in the ranges aboveaccording to the present disclosure are those surfactant compounds whichcontain a long chain hydrocarbon hydrophobic group in their molecularstructure and a hydrophilic group, including salts such as carboxylate,sulfonate, sulfate or phosphate groups. The salts may be sodium,potassium, calcium, magnesium, barium, iron, ammonium and amine salts ofsuch surfactants. Anionic surfactants include the alkali metal, ammoniumand alkanol ammonium salts of organic sulfuric reaction products havingin their molecular structure an alkyl, or alkaryl group containing from8 to 22 carbon atoms and a sulfonic or sulfuric acid ester group.Examples of such anionic surfactants include water-soluble salts ofalkyl benzene sulfonates having between 8 and 22 carbon atoms in thealkyl group, alkyl ether sulfates having between 8 and 22 carbon atomsin the alkyl group and 2 to 9 moles ethylene oxide in the ether group.Other anionic surfactants include alkylsulfosuccinates, alkylethersulfosuccinates, olefin sulfonates, alkyl sarcosinates, alkylmonoglyceride sulfates and ether sulfates, alkyl ether carboxylates,paraffinic sulfonates, mono and di-alkyl phosphate esters andethoxylated derivatives, acyl methyl taurates, fatty acid soaps,collagen hydrosylate derivatives, sulfoacetates, acyl lactates,aryloxide disulfonates, sulfosucinamides, naphthalene-formaldehydecondensates and the like. Aryl groups generally include one and tworings, alkyl generally includes from 8 to 22 carbon atoms and the ethergroups generally range from 1 to 9 moles of ethylene oxide (EO) and/orpropylene oxide (PO), preferably EO. Specific anionic surfactants whichmay be selected include linear alkyl benzene sulfonates, includingwithout limitation those such as decylbenzene sulfonate, undecylbenzenesulfonate, dodecylbenzene sulfonate, tridecylbenzene sulfonate,nonylbenzene sulfate and the sodium, potassium, ammonium, triethanolammonium and isopropyl ammonium salts thereof.

Nonionic surfactants may also be present in a composition according tothe disclosure in combination with a hamelia patens extract or any ofits components independently present in any amount specified within theranges above. The nonionic surfactant (s) may be any of the knownnonionic surfactants which, as with other surfactants discussed herein,are generally selected on the basis of compatibility, effectiveness andeconomy and present in a composition according to the disclosure ineffective amount to enhance wettability or permeability of mammalianskin when applied thereto or to otherwise beneficially modify activityof components present in a combination provided herein. Examples ofuseful nonionic surfactants include without limitation condensates ofethylene oxide with a hydrophobic moiety which has an averagehydrophilic lipolytic balance (HLB) between about 8 to about 16, and insome embodiments between about 10 and about 13. Nonionic surfactantsinclude the ethoxylated primary or secondary aliphatic alcohols havingfrom about 8 to about 24 carbon atoms, in either straight or branchchain configuration, with from about 2 to about 40, and in someembodiments between about 2 and about 9 moles of ethylene oxide per moleof alcohol. Other suitable nonionic surfactants include the condensationproducts of from about 6 to about 12 carbon atoms alkyl phenols withabout 3 to about 30, and preferably between about 5 to about 14 moles ofethylene oxide.

Many cationic surfactants are known in the art and almost any cationicsurfactant having at least one long chain alkyl group of about 10 to 24carbon atoms is suitable for optional use as a component in acomposition which includes a hamelia patens extract according to thepresent disclosure.

Other optional ingredients or additives which may be used in combinationwith hamelia patens extract in formulating compositions according to thepresent disclosure include pH adjusting chemicals, for example,loweralkanolamines such as monoethanolamine (MEA) and triethanolamine(TEA). Sodium hydroxide solutions may also be utilized as an alkaline pHadjusting agent. The pH adjusting chemicals function to neutralizeacidic materials that may be present. Mixtures of more than one pHadjusting chemical can also be utilized.

Phase regulants (well known liquid detergent technology) may also beoptionally present in a composition of the disclosure. These can berepresented by lower aliphatic alcohols having from 2 to 6 carbon atomsand from 1 to 3 hydroxyl groups, ethers of diethylene glycol and loweraliphatic monoalcohols having from 1 to 4 carbon atoms and the like.

Detergent hydrotropes may also be included in a composition according tothe disclosure. Examples of detergent hydrotropes include salts ofalkylarylsulfonates having up to 3 carbon atoms in the alkyl group e.g.,sodium, potassium, ammonium, and ethanolamine salts of xylene, toluene,ethylbenzene, cumene, and isopropylbenzenesulfonic acids.

Other optional supplemental additives include de-foamers such as highmolecular weight aliphatic acids, especially saturated fatty acids andsoaps derived from them, dyes and perfumes; fluorescent agents oroptical brighteners; suspension stabilizing agents; antioxidants;softening agents; uv-light inhibitors or absorbers; preservatives;polyacids, opacifiers, and bacteriacides.

An inorganic or organic builder may optionally be added in small amountsto a composition according to some embodiments of the disclosure.Examples of inorganic builders include water-soluble alkali metalcarbonates, bicarbonates, silicates and crystalline and amorphousalumino-silicates. Examples of organic builders include the alkalimetal, alkaline metal, ammonium and substituted ammonium polyacetates,carboxylates, polycarboxylates, polyacetyl carboxylates and polyhydroxysulfonates.

Hamelia patens extracts of the present disclosure are useful inproviding compositions which contain materials typically known to andused by those skilled in the art of formulation as being useful informulating skin-care compositions, shampoos and other products,particularly, but not limited, to products intended for topicalapplication. For purposes of this disclosure, the words “materialstypically known to and used by those skilled in the art of formulation”means one, or any combination comprising more than one of the materialsselected from the group consisting of: fatty acids, alkyl sulfates,ethanolamines, amine oxides, alkali carbonates, water, ethanol,isopropanol, pine oil, sodium chloride, sodium silicate, polymers,alcohol alkoxylates, zeolites, aloe, vitamins, emu oil, anti-oxidants,carotenoids, terpenoids, flavonoids, hormones, perborate salts, alkalisulfates, enzymes, hydrotropes, dyes, fragrances, preservatives,brighteners, builders, polyacrylates, essential oils, alkali hydroxides,ether sulfates, alkylphenol ethoxylates, fatty acid amides, alpha olefinsulfonates, paraffin sulfonates, betaines, chelating agents, tallowamineethoxylates, polyetheramine ethoxylates, ethylene oxide/propylene oxideblock copolymers, alcohol ethylene oxide/propylene oxide low foamsurfactants, methyl ester sulfonates, alkyl polysaccharides, N-methylglucamides, alkylated sulfonate diphenyl oxide, and water solublealkylbenzene sulfonates or alkyltoluene sulfonates, each present whenselected in conventionally-used amounts.

In one embodiment, any hamelia patens extract of the present disclosuremay be present in facial and body cleansing compositions. Thesecleansing compositions may also comprise a fatty acid soap together withother non-soap surfactants, such as mild synthetic surfactants. Body andfacial cleaning compositions may also generally include a moisturizer oremollient and polymeric skin feel and mildness aids. The compositionsmay further optionally include thickeners (e.g., magnesium aluminumsilicate, carbopol), conditioners, water soluble polymers (e.g.,carboxymethyl cellulose), dyes, hydrotropes brighteners, perfumes, andgermicides.

In some embodiments, any extract of hamelia patens of the presentdisclosure may be present in a shampoo. The shampoo composition may alsocomprise one or more other surfactants, optionally a compound considereduseful for treating dandruff, such as selenium sulfide, a suspendingagent, an amide, nonionic polymer material for aiding in dispersingparticles, nonvolatile silicone fluid, and a variety of othernonessential components suitable for rendering the composition moreformulatable, such as preservatives, viscosity modifiers, pH adjustingchemicals, perfumes, and dyes.

In other embodiments, any hamelia patens extract of the presentdisclosure may be present in a light-duty detergent composition. Thelight duty detergent composition may further include one or more othersurfactants, opacifiers (e.g. ethylene glycol di-stearate), thickeners(e.g. guar gum), antimicrobial agents, anti-tarnish agents, heavy metalchelators (e.g. EDTA), perfumes and dyes.

In further embodiments, any hamelia patens extract of the presentdisclosure may be present in a heavy-duty detergent composition. Theheavy duty detergent composition may also include one or more othersurfactants, an electrolyte (i.e. water soluble salt), enzymes with orwithout stabilizers such as calcium ion, boric acid, propylene glycoland/or short chain carboxylic acids, and conventional alkalinedetergency builders.

In yet other embodiments, any hamelia patens extract of the disclosuremay be present in a conditioner composition that comprises alkylaminecompounds.

In other embodiments, any hamelia patens extract of the presentdisclosure may be present in a cosmetic composition, such as lipstick,and including lip balms. The cosmetic composition may further include atleast one polymer thickening agent, one or more chemical preservativesor water activity depressants to prevent microbial spoilage, asun-screening agent such as p-aminobenzoic acid, cinnamic acidderivatives, and a vehicle. The vehicle can include any diluent,dispersant or carrier useful in ensuring an even distribution of thecomposition when applied to skin and may include water, an emollientsuch as an alcohol or oil, a propellant for example, trichloromethane,carbon dioxide or nitrous oxide, a humectant, and a powder such aschalk, talc, and starch.

From the foregoing it is evident that the disclosure providescompositions in which a hamelia patens extract is present. Thesecompositions and others evident from this disclosure are efficacious ina wide range of therapeutic and cosmetic end uses.

One such end use for a composition comprising a hamelia patens extractaccording to the disclosure is in providing components present inhamelia patens extract to be present on clothing, such as by employing alaundry detergent formulation according to the disclosure, which canprovide components of the hamelia patens extract to affected areasincluding the torso and extremities of skin areas.

Another end use for a composition comprising a hamelia patens extractaccording to the disclosure is in providing dental pastes, dentrifices,oral ointments, colloidal suspensions and gels containing hamelia patensextract which can be applied to inflamed, lacerated, or other affectedor symptomatic areas on the gums for relief from aphthous ulceration,gum papillae, mouth lesions, tissue flaps, wounds, and angular chelitisof the mouth and/or lips.

Another end use for a composition comprising a hamelia patens extractaccording to the disclosure is in the field of ophthalmology. Extractsand compositions according to the disclosure are useful in treatingcataracts, pteregium, conjunctival pterygium, photokeratitis,keratopathy and other conditions caused by solar radiation. Medicationsthat can be adapted to use for the areas surrounding the eye in order tominimize or avoid irritation when treating skin adjacent to eye lidsthat have solar damage. For such embodiments a hamelia patens extract isput up in a vehicle that is opthamologically-acceptable, including thepresence of appropriate buffers and absence of materials that tend tocause irritation or inflammation.

Another end use for a composition comprising a hamelia patens extractaccording to this disclosure is in the field of treatment of skinconditions, including cancer-related skin conditions, includingsuperficial basal cell carcinomae, squamous cell carcinomae, malignantmelanoma, Kaposi's sarcoma, cutaneous lymphomae, and Merkel cellcarcinomae. In some embodiments, a salve, crème, ointment, emulsion, orlotion containing an extract of hamelia patens according to thedisclosure may be applied topically to an affected area, with gentlerubbing. In some embodiments, a salve, crème, ointment, or lotionincluding a hamelia patens extract according to the disclosure isapplied once daily to such an affected area. In other embodiments, asalve, crème, ointment, or lotion including a hamelia patens extractaccording to the disclosure is applied twice daily to such an affectedarea. In another embodiment, a salve, crème, ointment, or lotionincluding a hamelia patens extract according to the disclosure isapplied thrice daily to such an affected area. In another embodiment, asalve, crème, ointment, or lotion including a hamelia patens extractaccording to the disclosure is applied four times daily to such anaffected area. In other embodiments, a salve, crème, ointment, or lotionincluding a hamelia patens extract according to the disclosure isapplied more than four times daily to such an affected area.

Another end use for a hamelia patens extract according to thisdisclosure is in the field of treatment of pre-cancerous skinconditions, by topical application of hamelia patens extract. In someembodiments, a salve, crème, ointment, or lotion including hameliapatens extract according to the disclosure is applied to such a selectedarea of mammalian skin. A salve, crème, ointment, or lotion includinghamelia patens extract according to the disclosure can be applied tomammalian skin on a maintenance schedule once or more times daily toprevent recurrence of cancerous lesions in individuals with extensivesun damage, history of multiple skin cancers and pre-cancerous growths,and areas following Moh's surgery for multi-centric lesions.

Compositions according to the disclosure comprising an extract ofhamelia patens intended for topical application to skin in someembodiments include additional substances for enhancing transdermalabsorption, including without limitation phosphatidyl cholines such aslecithin, water, alcohols, glyceryl ester oils, and dimethylsulfoxide,present in effective transdermal absorption-enhancing amounts. In someembodiments, a salve, crème, ointment, or lotion including an extract ofhamelia patens according to the disclosure is applied once daily to anarea of skin showing no symptoms of any disorder, in a preventativecapacity. In other embodiments, a salve, crème, ointment, or lotionincluding an extract of hamelia patens according to the disclosure isapplied once daily to a pre-cancerous lesion. In other embodiments, asalve, crème, ointment, or lotion including an extract of hamelia patensaccording to the disclosure is applied at least twice daily to apre-cancerous lesion or a normal area present on skin. A normal areapresent on skin is one which has no evidence of any abnormal conditionas viewed by the naked eye. In other embodiments, a salve, crème,ointment, or lotion including an extract of hamelia patens according tothe disclosure is applied at least thrice daily to a pre-cancerouslesion or a normal area present on skin. In other embodiments, a salve,crème, ointment, or lotion including an extract of hamelia patensaccording to the disclosure is applied at least four times daily to apre-cancerous lesion or a normal area present on skin. In otherembodiments, a salve, crème, ointment, or lotion including an extract ofhamelia patens according to the disclosure is applied more than fourtimes daily to a pre-cancerous lesion or a normal area present on skin.In some embodiments, a salve, crème, ointment, or lotion including anextract of hamelia patens according to the disclosure is applied twicedaily to a pre-cancerous lesion or a normal area present on skin forabout two weeks. The dry, scaly, whitish to localized reddening area ofsolar keratosis is replaced by new pink skin growth. In some instances akeratotic area may re-cur. In such instances the topical application ofa composition comprising an extract of, or components of an extract of,hamelia patens extract present in a vehicle according to the disclosureis repeated, as no detrimental effects have been observed in so doing,the hamelia patens extract being benign and innocuous.

Other end uses for an extract of hamelia patens according to thisdisclosure are in the field of enhancing healing of skin that is worn ordamaged from various environmental and other effects (includingartificial “tanning beds” present in tanning salons) by topicalapplication of a salve, crème, ointment, or lotion including an extractof hamelia patens according to the disclosure, also including reversalof skin aging, skin wrinkling, alleviating symptoms induced by externalbeam irradiation such as resulting from treating cancers with radiation,anti-fungal effect on skin, treatment of external hemorrhoids, treatmentof sunburns and other ultraviolet light-induced skin conditions,treatment of autoimmune disorders including without limitationpsoriasis, eczema, chronic skin ulceration, chronic dermatitis, animalbites including cat bites, venous stasis ulceration, cuts, insect bites,skin inflammation, skin rashes, diaper rash, and rosacea.

Other end uses for an extract of hamelia patens according to thisdisclosure are in the field of internal medicine, wherein a crystallineextract of hamelia or alternatively components present in hamelia patensextract are administered systemically, such as by an oral preparation orby injection. In one embodiment a composition containing components ofhamelia patens extract is administered orally in an effective amount toexert anti-inflammatory and/or anti-neoplastic effects on epitheliallayers of the esophagus, which is of benefit for cases of inflammationsassociated with esophageal reflux, esophageal ulceration, andcarcinogenic exposures. Moreover, the present disclosure provides nasalspray or drops useful for treatment of allergic rhinitis, byincorporation of a hamelia patens extract according to the disclosureinto a conventional nasal spray or nasal drop formulation at any amountof between about 0.05% and about 20% by weight based on the total weightof the composition, including all percentages and ranges of percentagestherebetween.

In another embodiment, a salve, crème, ointment, or lotion containing ahamelia patens extract according to the disclosure is also applied toskin following Mohs surgery for invasive skin malignancies.

The present disclosure provides eye drops useful for administration intothe eyes, by incorporation of a hamelia patens extract according to thedisclosure into a conventional isotonic eyedrop formulation at anyamount of between about 0.05% and about 5% by weight based on the totalweight of the composition, including all percentages and ranges ofpercentages therebetween. Such eyedrop formulations include the presenceof known buffers, to control pH to be at a level that isopthamologically-acceptable.

Below are set forth several examples which shall be interpreted as beingexemplary of various embodiments of this disclosure and shall not beconstrued as delimitive thereof in any way.

Example I Petrolatum Extract of Hamelia patens

A one-liter volume of cut and cleaned leaves of hamelia patens arecompressed and combined with about 125 ml of petrolatum, the mixturebeing heated to about 65 degrees centigrade for about 10 minutes. Theleafy material is mechanically separated from the petrolatum, which isoptionally filtered, to afford a petrolatum-borne extract of the planthamelia patens.

Example II Aqueous Alcohol Extract of Hamelia patens

500 grams of ground Hamelia Patens leaves are combined with 500 ml of asolvent mixture that contains 10% by volume of ethanol in water. Theliquid is maintained at room temperature for 30 minutes with occasionalstirring of the leaves and solvent. The resulting solution iscentrifuged to remove solids and filtered to provide a liquid extract ofhamelia patens in solution.

Example III Crystalline Extract of Hamelia patens

The liquid extract provided in Example II is placed in a vacuum still,heated to fifty degrees centigrade, and subjected to reduced pressure of300 ton with a slow sweep of nitrogen gas being admitted over the liquidto enhance removal of solvent, the pressure being maintained at 300 ton.Once the solvent has been removed, a crystalline extract of hameliapatens remains. This extract is optionally purified viare-crystallization using an ethanol-water mixture.

Example IV Lotion

Five grams of the crystalline extract provided in Example III wereplaced in a 150 ml beaker. Ninety five grams of Vaseline® moisturelocking lotion (unfragranced) were subsequently added to the beaker, andthe contents mixed by mechanical means until the extract wassubstantially evenly dispersed within the lotion to provide a lotioncontaining 5% of an extract of the plant hamelia patens.

Example V Vitamin-Fortified Lotion

To forty five grams of the Lotion of example V placed in a 100 ml beakerare added five grams of Vitamin E oil and the beaker contents mixeduntil at least substantially uniform to provide a Vitamin-fortifiedlotion.

Example VI Lotion Concentrate

Fifty grams of the crystalline extract provided in Example III wereplaced in a 150 ml beaker. Fifty grams of Vaseline® moisture lockinglotion (unfragranced) were subsequently added to the beaker, and thecontents mixed by mechanical means until the extract was substantiallyevenly dispersed within the lotion to provide a lotion containing 50% ofan extract of the plant hamelia patens. This lotion may be used as alotion concentrate suitable as a base stock from which other lotions maybe produced.

Example VII Laundry Detergent

A conventional particulate laundry detergent (CHEER® detergent) isdisposed on a moving web which may be a conveyor belt and a spray nozzleis disposed above the moving particulate laundry detergent product. Thespray nozzle is fed by a solution comprising the extract of Example II,which is sprayed onto the moving detergent powder in a concentration andrate sufficient to provide a laundry detergent comprising an extract ofthe plant hamelia patens at about 1% by weight.

Example VIII Laundry Detergent

A conventional particulate laundry detergent (CHEER® detergent) isdisposed on a moving web which may be a conveyor belt and a spray nozzleis disposed above the moving particulate laundry detergent product. Thespray nozzle is fed by a solution comprising the extract of Example II,which is sprayed onto the moving detergent powder in a concentration andrate sufficient to provide a laundry detergent comprising an extract ofthe plant hamelia patens at about 10% by weight. This product may beused as is, or used as a concentrate from which other detergents may beproduced by blending.

Example IX Salve Containing Hamelia patens

To 95 grams of a petrolatum-based extract of the plant hamelia patensprepared according to example I, are added five grams of DMSO and 0.5grams of soy lecithin. The mixture is blended until at leastsubstantially uniform to provide a salve having enhanced transdermalmobility.

Example X Hand Soap

Five grams of the crystalline extract of hamelia patens extractaccording to example III are placed in a 150 ml beaker and blended withninety five grams of SOFTSOAP® Elementals (Colgate-Palmolive) until atleast substantially-homogeneous.

Example XI Injectable Solution

Five grams of purified extract of the hamelia patens plant according toexample III are combined with 95 grams of a 0.9% (wt.) saline solution.After mixing, the composition is sterilized and put up into ampoules inthe usual manner. This solution may be injected into the basal layer ofthe dermis at any selected location, including into the base of any formof skin cancer, pre-cancerous lesion, isolated and/or skin lesions orgrowths.

Example XII Dental Paste

abrasive 40% (wt.) glycerol 20% sorbitol 25% propylene glycol 3.0%hydroxyethyl cellulose 1.0% sodium lauryl sulfate 1.0% methylp-hydroxybenzoate 0.1% saccharin sodium 1.0% flavor 0.9% alkali metalhalide 0.5% crystalline extract from to example III 7.5%

The above ingredients are combined in the usual manner to provide adental paste.

Example XIII Oil in Water Emulsion

fatty alcohols (50/50 mix C16 + C18) 15 grams mineral oil 10 gramspetrolatum  3 grams PEG-15 (oleyl.cetyl alc.)  5 grams water 67 gramscrystalline extract from to example III 7.5 grams 

Example XIV Treatment for Solar Keratosis

A 70 year old man having a history of multiple skin cancers excised fromhis hands in the past, presented with multiple solar keratosis lesionson the back of both hands. The affected areas on this man's hands weretreated twice daily with a petroleum jelly extract according to exampleI. After a three-week period, the lesions had essentially disappeared.Preventive treatment with the petrolatum extract has kept the lesionsfrom re-appearing for over a year of repeated prophylactic treatment.The treatment has shown no adverse reactions nor any indications oftoxicity.

Example XV Treatment for Solar Keratosis

Three men in their eight decade of life each having multiple solarkeratosis lesions present on their forearms were each treated twicedaily by application of a petroleum jelly extract according to exampleIto the affected areas for a three-week period, after which the lesionshad essentially disappeared, with only faint traces of the originallesions remaining. The treatment showed no adverse reactions orindications of toxicity.

In addition, a hamelia patens extract also has anti-microbial,anti-bacterial, anti-inflammatory, anti-septic, and wound healingpromoting properties. It is further anticipated by this disclosure thatan extract of hamelia patens has anti-prion activity and anti-viralactivity and a composition as described herein is accordingly useful fortreating conditions such as warts, shingles, herpes I, herpes II, humanpapilloma virus (HPV), and other viruses by topical application,injection, oral administration, or ocular administration. Accordingly,extracts and compositions herein described are useful in various formsrecognizable by those skilled in this art after reading thisspecification and the claims appended hereto to treat any disorderinvolving microbes, inflammation, wounds, and anti-sepsis. In oneembodiment, an extract according to example III above is dissolved inethanol/water mixture to form a composition which is subsequentlyadsorbed onto a substrate, including without limitation cellulosicsubstrates, sponges, and SAP polymer substrates. For the cases where asponge is employed, this provides a convenient means to dispense smallamounts of the material to another substrate, such as the hands, orobjects such as pens, pencils etc. In one embodiment such a spongelatent with hamelia patens extract is contained in an enclosure having afirst and second end, each of said ends having a hole disposedtherethrough, through which is passed an article such as a toothbrush,pen or pencil, which during its travel through such enclosure is coatedwith hamelia patens extract in sufficient quantity to effectivelydeactivate or kill microbes present on the surface of such pen orpencil. By extension, such an article is useful for cleaning otherimplements, including surgical tools.

Hamelia patens extracts as provided herein, whether present incrystalline form or liquid form, including oil-based liquids, aqueousliquids or alcohol-water mixtures, etc., as described, are useful incombination with liposomes. Suitable liposomes include those recognizedby those skilled in the art as being useful in combination withplant-derived extracts and components present therein as hereindescribed to enhance delivery of such extracts or components to, into,onto, or within the body of a mammalian subject. Liposomes includeartificial microscopic vesicles consisting of an aqueous core presentand enclosed within either one, or a plurality of phospholipid layers,which structured materials are useful to convey one or any combinationincluding any number greater than one components present in hameliapatens extract to target cells or organs of a mammalian subject.

Hamelia patens extracts as provided herein, whether present incrystalline form or liquid form, including oil-based liquids, aqueousliquids or alcohol-water mixtures, etc., as described, are useful incombination with nanoparticles. As used herein, a nanoparticle is anyparticulate form that is less than about one micrometer in at least onedimension, including particulate forms that are less than one micrometerin at least one dimension. Suitable nanoparticles include thoserecognized by those skilled in the art as being useful in combinationwith plant extracts and materials present in plant-derived extracts, andinclude without limitation such nanoparticles as: solid corenanoparticles, hollow core nanoparticles, lipid nanoparticles, PEGnanoparticles, chitosan nanoparticles.

Although this invention has been described and disclosed in relation tovarious embodiments, modifications, combinations, and alterations of thefeatures of various embodiments disclosed may become apparent to personsof ordinary skill in this art after reading and understanding theteachings of this specification, drawings, and the claims appendedhereto. The present disclosure includes subject matter defined by anycombinations of any one (or more) of the features, elements, or aspectspresent described in reference to any embodiment described in thisdisclosure with one or more feature(s), element(s), or aspect(s)described in relation to any other one (or more) other embodimentsdescribed. These combinations include the incorporation of the featuresand/or aspect(s) of any dependent claim, singly or in combination withfeatures and/or limitations of any one or more than one of the otherdependent claims, with features and/or limitations of any one or morethan one independent claim(s), with the remaining dependent claims intheir original text being read and applied to any independent claim(s)so modified. These combinations also include combination of the featuresand/or limitations of one or more of the independent claims withfeatures and/or limitations of another one or more than one of theindependent claims to arrive at a modified independent claim, with theremaining dependent claims in their original text or alternately asmodified per the foregoing, being read and applied to any independentclaim(s) so modified.

1. A method for alleviating signs of radiation dermatitis induced byclinical exposure to external beam irradiation on the skin of amammalian subject, which method comprises contacting a compositioncontaining a hamelia patens extract to an affected skin area of saidsubject in an effective amount and frequency for reducing said symptoms.2. The method according to claim 1, wherein said composition is in anyform selected from the group consisting of: salves, creams, ointments,and lotions.
 3. The method according to claim 1 wherein said compositioncomprises any carrier selected from the group consisting of: water;saline solution, any C1 to C4 alcohol; any glyceryl ester oil; and anymineral oil.
 4. The method according to claim 1 wherein said compositioncomprises a pharmaceutically-acceptable carrier.
 5. The method accordingto claim 1 wherein said extract is an aqueous extract.
 6. The methodaccording to claim 1 wherein said extract is a non-aqueous extract. 7.The method according to claim 1 wherein said composition comprises ananoparticle.
 8. The method according to claim 7 wherein saidnanoparticle is selected from the group consisting of solid corenanoparticles, hollow core nanoparticles, lipid nanoparticles, PEGnanoparticles, and chitosan nanoparticles, including mixtures thereof.9. The method according to claim 1 wherein said composition comprises aliposome.
 10. The method according to claim 1 wherein said extractcomprises an effective symptom-reducing amount of at least one materialselected from the group consisting of: alkaloids, 2-alpha-hydroxyursolicacid, apigenin-7-o-beta d-glucuronide, aricine, catequine,19-alphahydroxy Asiatic acid, 24-methylenecycloartane-3β-ol,24-methylcycloart-24-en-3β-ol, 2E-3,7,11,15,19-pentamethyl-2-eicosane-1-ol, ephedrine, flavonones,2′-5-5′-7-tetrahydroxy-7-o-rutinoside, isomaruquine, isopteropodine,maruquine, the methyl ester of maruquine, mitraphylline, narirutin,narirutin (2r), narirutin (2s), oxindole alkaloids, oxindole aricine,palmirine, pigenin-7-o-beta D-glucuronide, pomolic acid, pteropodine,rumberine, rosmarinic acid, rotundic acid, rumberine, rutin,seneciophylline, β-sitosterol, speciophylline, stigmast-4-en-3-3-dione,stigmast-4-en-3-6-dione, stigmasterol, tannins, tormentic acid, uncarineF, and ursolic acid, including any mixtures thereof.
 11. The methodaccording to claim 10 wherein said composition comprises all of saidmaterials recited in said group.
 12. The method according to claim 10wherein each material selected to be present in said composition isindependently selected to be present in any amount between 0.05% byweight and 30% by weight based on the total weight of said composition.13. A method according to claim 1 wherein said external beam irradiationis substantially of a single frequency.
 14. A method according to claim1 wherein said external beam irradiation is a plurality of frequencies.15. A method according to claim 1 wherein the daily amount of saidexternal beam irradiation used to treat the subject is any amount in therange of 1.8 to 2.2 Gy per day.
 16. A method according to claim 15wherein said daily amount of radiation is applied on a repeat, dailybasis to said subject.
 17. A method according to claim 1 wherein thesource of said external beam irradiation is derived from emissions of aradioactive isotope of any element selected from the group consistingof: cobalt, cesium, iodine, platinum, and yttrium.
 18. A methodaccording to claim 1 wherein the source of said external beamirradiation is derived from photons.
 19. A method according to claim 18wherein said photons are infrared photons.
 20. A method according toclaim 1 wherein said external beam irradiation was administered to saidsubject as a medical treatment.